Leukostim - Instructions For Use, Reviews, Price, Drug Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Leucostim

Leukostim: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. Drug interactions
12. 12. Analogs
13. 13. Terms and conditions of storage
14. 14. Terms of dispensing from pharmacies
15. 15. Reviews
16. 16. Price in pharmacies

Latin name: Leucostim

ATX code: L03AA02

Active ingredient: filgrastim (filgrastim)

Manufacturer: Biocad, CJSC (Russia)

Description and photo update: 2019-02-09

Prices in pharmacies: from 2100 rubles.

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Leukostim is an immunomodulator.

Release form and composition

Dosage form - solution for intravenous and subcutaneous administration: colorless or yellowish, transparent (150 μg / ml - 1 ml each in vials, 1 or 5 vials in a blister pack, 1 package in a cardboard box; 300 μg / ml - 1 or 1.6 ml in vials, 1 or 5 vials in a blister strip packaging, 1 package in a cardboard box; 0.5 or 1 ml each in syringes with plungers and soldered needles, 1 or 5 syringes in a cardboard box; 600 μg / ml - 0.8 ml in syringes with plungers and soldered needles, 1 or 5 syringes in a contour cell package, 1 package in a cardboard box; each pack also contains instructions for the use of Leukostim).

Active substance: filgrastim, in 1 ml of solution - 150 μg (15 million IU), 300 μg (30 million IU) or 600 μg (60 million IU) (IU - international units).

Auxiliary components: water for injection, glacial acetic acid, sodium acetate trihydrate, polysorbate 80, dextran 60,000, mannitol.

Pharmacological properties

Pharmacodynamics

The active substance of Leukostim, filgrastim, is a highly purified non-glycosylated protein, consisting of 175 amino acids. It is produced by a strain of Escherichia coli, into the genome of which the gene for G-CSF (human granulocyte colony-stimulating factor) has been introduced using genetic engineering methods. Human G-CSF is a glycoprotein that regulates the production of functionally active neutrophils and their release from the bone marrow into the blood.

As a result of the use of Leukostim for 24 hours after administration, the number of neutrophils in the peripheral blood increases significantly with a slight increase in the number of monocytes. In TCN (severe chronic neutropenia), filgrastim can lead to a slight increase in the number of circulating basophils and eosinophils. Some of these patients may have basophilia or eosinophilia even before starting treatment.

Filgrastim dose-dependently increases the number of neutrophils with normal / increased phagocytic and chemotactic activity. After the end of therapy, the number of neutrophils in the peripheral blood decreases by 50% in 1–2 days, the indicator returns to normal levels within the next 1–7 days.

The use of Leukostim can significantly reduce the frequency, duration and severity of neutropenia and febrile neutropenia, while reducing the need and duration of inpatient treatment in patients receiving chemotherapy with cytostatics or myeloablative treatment followed by bone marrow transplantation.

Patients receiving Leucostim and cytotoxic chemotherapy require lower doses of antibiotics compared to patients receiving cytotoxic chemotherapy without filgrastim.

With the use of the drug, the duration of febrile neutropenia, the need for antibiotic therapy and hospitalization after induction chemotherapy in patients with acute myeloid leukemia are significantly reduced. At the same time, filgrastim has no effect on the frequency of fever and infectious complications.

The use of Leukostim, both independently and after the end of chemotherapy, promotes the mobilization of the release of hematopoietic stem cells into the peripheral bloodstream. Allogeneic or autologous transplantation of PSCC (peripheral blood stem cells) is performed after therapy with high doses of cytostatics, or instead of / in addition to bone marrow transplantation. PSCC transplantation may also be prescribed after myelosuppressive cytotoxic treatment. The use of PSCCs mobilized with filgrastim can accelerate the restoration of hematopoiesis, reduce the risk of hemorrhagic complications and the need for platelet transfusion after myeloablative or myelosuppressive therapy.

The safety / efficacy profile of Leukostim in adults and children receiving cytotoxic chemotherapy does not differ.

In children and adults, against the background of congenital, periodic, idiopathic neutropenia, filgrastim steadily increases the number of neutrophils in the peripheral blood and reduces the incidence of infectious complications.

When Leukostim is prescribed to patients with HIV infection, it becomes possible to maintain a normal level of neutrophils and comply with the recommended doses of antiretroviral and / or other myelosuppressive therapy. There are no signs of increased HIV replication during filgrastim therapy.

Like other hematopoietic growth factors, G-CSF has a stimulating effect on human endothelial cells.

The carcinogenic properties of filgrastim have not been studied. Filgrastim does not cause mutations in the bacterial genome, regardless of the presence of the enzyme system necessary for the metabolism of the drug.

It has been found that certain malignant cells have G-CSF receptors on their surface. It cannot be ruled out that filgrastim can serve as a growth factor for various types of tumors.

In studies on rats of both sexes, when filgrastim was used in doses up to 500 μg / kg, no effect on fertility and pregnancy was found.

Filgrastim had no teratogenic effect in studies on rabbits and rats. In rabbits, there was an increased frequency of miscarriages, while fetal anomalies were not identified.

Pharmacokinetics

Filgrastim is rapidly absorbed after subcutaneous administration and reaches its maximum concentration in the blood serum in 2–8 hours. The half-life after intravenous or subcutaneous administration is usually in the range of 2-4 hours. The clearance and half-life are determined by the dose and the number of neutrophils. It can be assumed that the linear nature of clearance and pharmacokinetic processes predominate.

The absolute bioavailability after subcutaneous administration of 375 and 750 μg is 62% and 72%, respectively. Filgrastim concentration after cessation of its administration decreases to endogenous values within 24 hours.

In patients with oncological diseases and healthy volunteers before chemotherapy, with repeated administration of filgrastim, a decrease in its plasma concentration was revealed. The increase in substance clearance in this case is dose-dependent, presumably the degree of this increase depends on the degree of neutrophilia in the recipients. This is consistent with information about an increase in neutrophil-dependent clearance with an increase in the pool of neutrophils. In patients who receive filgrastim after chemotherapy, the plasma concentration of the substance remains at the same level until the beginning of hematopoiesis recovery.

With intravenous and subcutaneous administration of filgrastim, there is a positive linear relationship between dose and concentration in serum. After subcutaneous administration of therapeutic doses, the concentration of filgrastim exceeds 10 ng / ml for 8-16 hours. The volume of distribution is 150 ml / kg.

With long-term administration of filgrastim (up to 28 days) after autologous bone marrow transplantation, no cumulation and changes in the half-life are observed.

Regardless of the method of administration, excretion of filgrastim proceeds according to the rules of first-order kinetics. The half-life is 3.5 hours, the clearance is 0.6 ml / min / kg.

The pharmacokinetics of filgrastim in children after chemotherapy is similar to that in adults who receive the same dose of the drug based on body weight. This allows us to conclude that the pharmacokinetic processes of Leukostim are independent of age.

In end-stage renal disease, there is a tendency to an increase in systemic exposure to filgrastim compared with healthy volunteers and patients with creatinine clearance in the range of 30-60 ml / min.

Indications for use

Leukostim is used:

• Treatment of persistent neutropenia in patients with an advanced stage of the human immunodeficiency virus (HIV infection with an absolute neutrophil count ≤1.0x10 ⁹ / l) to reduce the risk of bacterial infections;
• Treatment of severe chronic neutropenia to reduce the incidence and duration of infectious complications, as well as to increase the number of neutrophils;
• Mobilization of hematopoietic progenitor cells into peripheral blood in healthy donors for their subsequent separation and allogeneic transplantation;
• Mobilization of hematopoietic progenitor cells into the peripheral blood for their subsequent separation and transplantation after myelosuppressive chemotherapy;
• Reducing the duration of grade II-IV neutropenia and a decrease in the incidence of febrile neutropenia in patients with nonmyeloproliferative neoplasms after chemotherapy with cytostatic drugs;
• Reducing the duration of neutropenia and prevention of complications caused by its development in patients receiving myeloablative chemotherapy with subsequent bone marrow transplantation.

Contraindications

Absolute:

• Kostmann's syndrome (severe congenital neutropenia) with cytogenetic disorders;
• Use in order to increase doses of cytotoxic chemotherapy drugs in excess of the recommended ones;
• Simultaneous use with cytotoxic chemotherapy and radiation therapy;
• Lactation period;
• Individual intolerance to the components of the drug.

Relative (Leucostim is prescribed with caution):

• Sickle cell anemia;
• Bone pathology (including osteoporosis);
• Secondary acute myeloid leukemia (associated with limited safety / efficacy data);
• Use in combination with high-dose chemotherapy;
• Pregnancy.

Safety and efficacy has not been evaluated for:

• Children under 16 years of age after myelosuppressive or myeloablative therapy followed by autologous transfusion of PSCC;
• Newborns with severe chronic neutropenia.

Leukostim, instructions for use: method and dosage

Leucostim is administered subcutaneously (s / c) or intravenously (i / v). The route of administration and doses are determined individually by the attending physician, depending on the clinical situation. The subcutaneous route of administration is more preferred. If intravenous infusion is required, the drug is injected into a plastic container or vial with 5% dextrose solution. It is forbidden to use a 0.9% sodium chloride solution!

Do not dilute Leucostim to a final concentration of less than 2 μg / ml.

The duration of the intravenous infusion is 30 minutes.

Recommended doses of Leucostim:

• Treatment of neutropenia after a course of cytotoxic chemotherapy: s / c or i / v, 5 μg / kg body weight 1 time per day. For an adequate assessment of the effectiveness of treatment, it is recommended to count the number of neutrophils in the peripheral blood daily. The therapy should be continued until the number of neutrophils exceeds the expected minimum and reaches a normal value exceeding 2.0x10 ⁹ / L. The duration of treatment can be up to 12 days;
• Decrease in the duration of neutropenia and prevention of associated complications after myeloablative chemotherapy followed by bone marrow transplantation: s / c or i / v at a dose of 10 μg / kg of the patient's body weight. The first dose is given at least 24 hours after chemotherapy, and for bone marrow transplantation, no later than 24 hours after bone marrow infusion. After the maximum decrease in the number of neutrophils, depending on the dynamics of their number, the daily dose is adjusted. If the content of neutrophils in the peripheral blood exceeds 1.0x10 ⁹ / l for 3 consecutive days, the dose of Leukostim is reduced by 2 times. If the number of neutrophils drops below 1.0x10 ⁹ / l, the dose is increased again to 10 μg / kg. If the absolute number of neutrophils exceeds 1.0x10⁹ / l for 3 consecutive days, the drug is canceled;
• Mobilization of hematopoietic stem cells: sc in a daily dose of 5 μg / kg of body weight (for patients after myelosuppressive chemotherapy) or at a dose of 10 μg / kg (for patients who did not receive chemotherapy) daily for 5-7 days, depending on the rate of increase the number of leukocytes in peripheral blood and the effectiveness of separation. 1 day before the expected date of the first separation (4th day of Leukostim administration) and later (up to the day of the last separation), it is necessary to assess the number of neutrophils and leukocytes in the peripheral blood. Cytapheresis is performed if the number of leukocytes reaches 5x10 ⁹/ l of peripheral blood from the 5th day of drug administration. After each separation in the sample to be cryopreserved, the number of CD34 + cells and nucleated cells is counted. The introduction of Leukostim is stopped after reaching the number of cryopreserved CD34 + cells, sufficient for transplantation (not less than 2x10 ⁶ per kg of patient weight). The safety and efficacy of Leukostim in healthy donors over 60 years old and under 16 years old have not been studied;
• Severe chronic neutropenia: s / c daily at a daily dose of 12 mcg / kg of the patient's body weight (with congenital neutropenia) or 5 mcg / kg (with intermittent and idiopathic neutropenia). Treatment is continued until the number of neutrophils stably exceeds 1.5x10 ⁹ / l. Then select the minimum effective dose to maintain the achieved result. When carrying out maintenance therapy, Leukostim is administered daily for a long period. After 1-2 weeks, depending on the patient's response, the daily dose can be increased or decreased by 2 times. In the future, every 1-2 weeks the dose is adjusted to maintain the number of neutrophils in the range from 1.5x10 ⁹ / l to 10x10 ⁹ / l;
• Neutropenia associated with HIV infection: n / a daily 1 time per day. The initial dose is 1-4 μg / kg of body weight, it is used until the number of neutrophils is normalized (more than 2x10 ⁹ / l), usually it takes 2 days. If the initial dose is ineffective, it is increased to 5 μg / kg / day. After reaching the therapeutic effect, maintenance treatment is carried out at a dose of 1-4 μg / kg / day 2-3 times a week. In the future, individual dose adjustment and long-term treatment may be required to maintain the normal neutrophil count (> 2x10 ⁹ / L).

In children with cancer and severe neutropenia, the safety profile of Leucostim did not differ from that in adults. Therefore, children are prescribed doses similar to those of adult patients receiving cytotoxic or myelosuppressive chemotherapy.

In patients with severe hepatic or renal impairment, dose adjustment of Leucostim is not required, since their pharmacodynamic and pharmacokinetic parameters are similar to those in healthy volunteers.

Side effects

• Cardiovascular system: transient decrease in blood pressure;
• Musculoskeletal system: muscle and / or bone pain (usually mild or moderate), exacerbation of existing rheumatoid arthritis;
• Hematopoietic system: anemia, thrombocytopenia;
• Nervous system: headache, increased fatigue;
• Respiratory system: infiltrates in the lungs with the development of respiratory distress syndrome in adults (more often after chemotherapy regimens that include bleomycin; their relationship with the use of Leukostim is unclear);
• Digestive system: diarrhea, hepatomegaly;
• Laboratory indicators: a decrease in the number of platelets in the peripheral blood, a reversible increase in the levels of lactate dehydrogenase, alkaline phosphatase, uric acid, glutamyl transpeptidase in the blood plasma;
• Urinary system: dysuria (usually mild or moderate);
• Others: soreness at the injection site; rarely (more often after intravenous administration) - allergic reactions (about half of them usually occur with the introduction of the first dose), skin rash, vasculitis, enlarged spleen, ruptured spleen, vascular thrombosis.

Overdose

No cases of filgrastim overdose have been reported.

When conducting research on bone marrow transplantation, Leucostim was administered in daily doses up to 138 μg without developing toxic effects. 1-2 days after discontinuation of the drug, the number of circulating neutrophils usually decreases by 50% and returns to normal in 1-7 days.

special instructions

Treatment with Leukostim should be carried out only under the supervision of an oncologist or hematologist with experience in the use of such drugs. Before its appointment, such causes of the development of transient neutropenia as viral infections should be excluded.

Special attention should be paid to the diagnosis of severe chronic neutropenia in order to differentiate them from other hematological diseases such as myeloid leukemia, myelodysplasia, and aplastic anemia.

In chronic myeloid leukemia and myelodysplastic syndrome, the safety and efficacy of filgrastim have not been established. For patients with these diseases and with precancerous lesions of the myeloid hematopoietic line, the appointment of Leukostim is not recommended, because some tumor cells can carry a receptor for granulocyte colony-stimulating factor. For this reason, special attention should be paid to the differential diagnosis between the blast crisis of chronic myeloid leukemia and acute myeloid leukemia.

During therapy, it is necessary to constantly monitor the size of the spleen (by palpation of the abdomen). According to research data, when the dose of Leucostim is reduced, the enlargement of the spleen stops or at least slows down.

A small number (about 3%) of patients with Kostmann's syndrome who received filgrastim had leukemia and myelodysplastic syndrome - natural complications of this disease, the relationship of which with the use of the drug has not been established. If these complications develop, Leukostim should be canceled.

In rare cases (less than 5%) in patients undergoing treatment with filgrastim, hyperleukocytosis was noted (an increase in the number of leukocytes above 100x10 ⁹ / l), therefore, the number of leukocytes should be measured regularly. If they increase more than 50x10 ⁹ / l Leucostim must be canceled. If the drug is used to mobilize hematopoietic stem cells, it should be canceled when the leukocyte count rises above 70x10 ⁹ / L.

Approximately 12% of patients with initially normal cytogenetics showed abnormalities, including monosomy 7, on re-examination. If cytogenetic abnormalities are found in patients with severe congenital neutropenia, the benefits and risks of continuing therapy should be weighed. Every 12 months, it is necessary to carry out cytogenetic and morphological studies of the bone marrow.

It is important to bear in mind that Leucostim does not prevent anemia and thrombocytopenia, which are often the result of high-dose chemotherapy drugs. Therefore, during treatment after chemotherapy, the number of platelets and erythrocytes, as well as the level of hemoglobin, should be regularly measured.

Influence on the ability to drive vehicles and complex mechanisms

Considering the mechanism of the pharmacological action of filgrastim, its effect on the speed of psychomotor reactions and the ability to concentrate seems extremely unlikely.

Application during pregnancy and lactation

• Pregnancy: Leukostim can be used only after assessing the ratio of the expected benefit with the possible risk, the safety of use has not been established;
• Lactation period: use is contraindicated.

Pediatric use

The safety and efficacy profile has not been studied:

• Newborns with THN;
• Children under 16 years of age after myelosuppressive or myeloablative therapy followed by autologous transfusion of PSCC.

Drug interactions

Leukostim is pharmaceutically incompatible with 0.9% sodium chloride solution.

Given the increased sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy drugs, it is not recommended to use Leukostim 24 hours before the start of the chemotherapy course and at least 24 hours after its end. The safety and efficacy of filgrastim administration on the same day as cytotoxic chemotherapy drugs have not been established. It is known that 5-fluorouracil, when used simultaneously with filgrastim, increases the severity of neutropenia.

When using Leukostim to mobilize hematopoietic stem cells after chemotherapy, it should be borne in mind that long-term use of cytostatics such as carboplatin, melphalan, carmustine (BCNU) can reduce the efficiency of mobilization.

Analogs

The analogues of Leukostim are: Granogen, Grasalva, Leucita, Neupogen, Mielastra, Neipomax, Neurostim, Tevagrastim, Filegim.

Terms and conditions of storage

Keep out of the reach of children. Observe the temperature regime 2-8 ºС.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Leucostim

Reviews of Leukostim are few. The safety / efficacy of the drug is similar to that of analogs.

Price for Leucostim in pharmacies

The approximate price for Leucostim is:

• 150 μg / ml –1150–2900 rubles. (1 pc. 1 ml each) or 5060–5500 rubles. (5 pcs. 1 ml each);
• 300 mcg / ml - 2000–3500 rubles. (1 pc. 1 ml each) or 8,200-10,000 rubles. (5 pcs. 1 ml each);
• 600 μg / ml - 1890–2200 rubles. (1 pc. 0.8 ml).

Leucostim: prices in online pharmacies

Drug name Price Pharmacy

Leukostim 60 mlnIU / ml solution for intravenous and subcutaneous administration 0.8 ml 1 pc. RUB 2100 Buy

Leukostim 300 mcg / ml solution for intravenous and subcutaneous administration 1 ml 1 pc. 2200 RUB Buy

Leukostim 300 mcg / ml solution for intravenous and subcutaneous administration 1 ml 5 pcs. 8200 rub. Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!